The role of liver NKT cells in the regulation of peripheral immune responses (42.9)

Abstract

Abstract We have previously shown that the liver plays an important role in oral tolerance induction. The liver can transfer tolerance to OVA from OVA fed mice to naïve mice. In this study we employed an oral tolerance model by OVA feeding to further explore the mechanisms underlying the role of the liver in oral tolerance induction. OVA feeding, either high dose or low dose, expanded NKT cells in the liver which expressed higher levels of CD95L and PD-L1, a moderate level of PD-1 on the surface, peaked at the 2nd dose feeding in the high dose group and at the 3rd dose feeding in the low dose group. The Foxp3+CD4+CD25+ T regulatory cells (Treg) showed a slight increase in the livers and spleens in the low-fed group, but increased only in the livers in the high-fed group. OVA feeding inhibited NKT cell linked T cell proliferation in both low and high dose fed livers and spleens. Elispot assay revealed an increase in IL-4 and IFN-γ production in the low-fed mice, but increased IL-10 in the high-fed mice. Moreover, the DTH responses to OVA stimulation were increased markedly in the NKT−/− mice with high dose feeding, but showed no significant change in the PD-L1−/− mice compared to that in WT mice. Our results indicate that the liver NKT cells are important in OVA-induced oral tolerance, particularly in high dose feeding. The function of NKT cell appears to depend on CD95L and CD4+CD25+Treg, but not on the PD-1/PD-L1 pathway. IL-10 appears dominant in high dose feeding, while IL-4 and IFN-γ show importance in low dose feeding.